ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1331A>G (p.Asn444Ser) (rs730880159)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208202 SCV000264078 likely pathogenic Primary familial hypertrophic cardiomyopathy 2015-04-07 criteria provided, single submitter clinical testing
Center for Human Genetics,University of Leuven RCV000468249 SCV000886832 uncertain significance Hypertrophic cardiomyopathy 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000158797 SCV000208732 likely pathogenic not provided 2015-07-07 criteria provided, single submitter clinical testing p.Asn444Ser (AAT>AGT): c.1331 A>G in exon 14 of the MYH7 gene (NM_000257.2). The N444S mutation in the MYH7 gene has been reported in one Italian individual diagnosed with HCM and was absent in 384 chromosomes from healthy, Italian control individuals in this study (Roncarti R et al., 2011). Mutations in nearby residues (R442C, R442H, I443T, K450E, K450T) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. Furthermore, N444S was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, N444S in the MYH7 gene is interpreted as a disease-causing mutation. The variant is found in HCM panel(s).
Invitae RCV000468249 SCV000546228 likely pathogenic Hypertrophic cardiomyopathy 2016-07-02 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 444 of the MYH7 protein (p.Asn444Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 21302287, 24704860). ClinVar contains an entry for this variant (Variation ID: 181343). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). In summary, this rare variant has been reported in affected individuals and is predicted to affect protein function. In the absence of any functional or segregation data it has been classified as a Likely Pathogenic.

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